Pristane-induced arthritis in mice. V. Susceptibility to pristane-induced arthritis is determined by the genetic regulation of the T cell repertoire

Arthritis Rheum. 1998 Nov;41(11):2022-31. doi: 10.1002/1529-0131(199811)41:11<2022::AID-ART18>3.0.CO;2-P.

Abstract

Objective: Pristane-induced arthritis (PIA) is an experimental seropositive arthritis that is characterized by serologic and cellular immune abnormalities and is dependent on the presence of a competent CD4+ T cell population. We examined the regulation of PIA by genes of the major histocompatibility complex (MHC) and the Mls-1 loci to determine whether the selection of the T cells that infiltrate arthritic joints is a critical factor in disease susceptibility.

Methods: Genetic regulation of PIA was investigated using F1 hybrid and congenic strain analysis to determine the influence of MHC and Mls-1 genes. The T cell receptor Vbeta phenotypes of lymph node cells and T cells infiltrating arthritic joints were examined with 2-color flow cytometry and reverse transcription-polymerase chain reaction techniques.

Results: F1 hybrid offspring from 2 major PIA-susceptible strains (DBA/1 x BALB/c) were resistant to the induction of arthritis because of the interaction between genes of the MHC and the Mls-1 loci, which modified the T cell repertoire. This conclusion was supported by the observed resistance to PIA in BALB/ c-Mls-1a mice, where T cells expressing the Vbeta8.1 and Vbeta6 phenotypes were absent. The receptor phenotype of T cells infiltrating arthritic joints in DBA/1 mice was markedly skewed toward Vbeta8.1 and Vbeta6 compared with the population observed in lymph nodes from either PIA or normal control DBA/1 mice.

Conclusion: The data support the hypothesis that PIA is a T cell-mediated disease. While pristane causes a polyclonal T cell expansion that gives rise to lymphadenopathy, the development of arthritis in susceptible strains of mice occurs due to the preservation of specific T cell subsets with the capacity to infiltrate synovial joints.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alleles
  • Animals
  • Arthritis, Rheumatoid / chemically induced*
  • Arthritis, Rheumatoid / epidemiology
  • Arthritis, Rheumatoid / immunology*
  • CD3 Complex / genetics
  • Female
  • Flow Cytometry
  • Gene Expression Regulation / immunology
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / genetics
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / immunology
  • Hybridization, Genetic
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin Variable Region / immunology
  • Immunosuppressive Agents*
  • Incidence
  • Lymph Nodes / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred DBA
  • Mice, Nude
  • Phenotype
  • Reverse Transcriptase Polymerase Chain Reaction
  • Synovial Membrane / immunology
  • T-Lymphocyte Subsets / immunology*
  • Terpenes*

Substances

  • CD3 Complex
  • Immunoglobulin Variable Region
  • Immunosuppressive Agents
  • Terpenes
  • pristane